HMGB1
过继性细胞移植
生物
免疫学
炎症
细胞生物学
分泌物
调解人
细胞
视网膜
免疫系统
T细胞
内分泌学
生物化学
作者
Guomin Jiang,Deming Sun,Huan Yang,Qin Lu,Henry J. Kaplan,Hui Shao
摘要
Abstract It is largely unknown how invading autoreactive T cells initiate the pathogenic process inside the diseased organ in organ-specific autoimmune disease. In this study, we used a chronic uveitis disease model in mice—EAU—induced by adoptive transfer of uveitogenic IRBP-specific T cells and showed that HMGB1, an important endogenous molecule that serves as a danger signal, was released rapidly from retinal cells into the ECM and intraocular fluid in response to IRBP-specific T cell transfer. HMGB1 release required direct cell–cell contact between retinal cells and IRBP-specific T cells and was an active secretion from intact retinal cells. Administration of HMGB1 antagonists inhibited severity of EAU significantly via mechanisms that include inhibition of IRBP-specific T cell proliferation and their IFN-γ and IL-17 production. The inflammatory effects of HMGB1 may signal the TLR/MyD88 pathway, as MyD88−/− mice had a high level of HMGB1 in the eye but did not develop EAU after IRBP-specific T cell transfer. Our study demonstrates that HMGB1 is an early and critical mediator of ocular inflammation initiated by autoreactive T cell invasion.
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